Abstract: Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca2+ overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca2+ overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

Abstract: A new, simple, sensitive and accurate spectrophotometric method has been developed for the assay of metoprolol tartrate (MPT), which is based on the complexation of drug with copper(II) [Cu(II)] at pH 6.0, using Britton-Robinson buffer solution, to produce a blue adduct. The latter has a maximum absorbance at 675 nm and obeys Beer’s law within the concentration range 8.5-70 mg/mL. Regression analysis of the calibration data showed a good correlation coefficient (r = 0.998) with a limit of detection of 5.56 mg/mL. The proposed procedure has been successfully applied to the determination of this drug in its tablets. In addition, the spectral data and stability constant for the binuclear copper(II) complex of MPT (Cu2MPT2Cl2) have been reported.

Abstract: Although chronic sympathetic activation provides inotropic and chronotropic support to the failing heart, such activation may also have deleterious effects, including the direct cardiotoxic effects of catecholamines, activation of the renin-angiotensin-aldosterone system and an increase in myocardial oxygen demand. These observations indicate that β-blockade might be beneficial in the treatment of heart failure resulting from dilated cardiomyopathy or ischaemic heart disease. Carvedilol is a non-selective β-blocker acting on β1-, β2-, and α1-adrenoceptors. It possesses potent anti-oxidant and anti-apoptotic properties, along with neuroprotective, vasculoprotective, cardioprotective effects, and it has reduced overall mortality in patients with heart failure in controlled clinical trials. Its role in treating cardiomyopathy requires focus. The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic index in cancer therapy. The cardiotoxic risk increases with the cumulative dose and may lead to congestive heart failure and dilated cardiomyopathy in adults and in children. This review focuses on recent research regarding the beneficial effects of carvedilol in the treatment of dilated cardiomyopathy and to revisit the available evidence on the cardioprotection of carvedilol when associated with anthracycline and to explain the mechanisms underlying the benefits of their co-administration.

Abstract: Several, if not all adrenergic β-blockers (β-Bs), accumulate progressively inside secretory vesicles in a time- and concentration-dependent manner, and could be considered to be false neurotransmitters. This transmitter effect is most likely unrelated to their ability to block adrenergic receptors, but it could explain the delay in lowering arterial pressure in hypertensive patients. We have developed a new drug to monitor the accumulation of β-Bs inside living cells, RCTM-3, which fluoresces in the visible spectrum. Here we describe the procedure to synthesize this new compound, as well as its fluorescent properties, pharmacological profile and its accumulation inside the secretory vesicles of PC12 cells.

Abstract: Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-inflammatory drug. This study was designed to evaluate whether carvedilol exerts a protective role against inflammation-mediated cardiotoxicity in the daunorubicin (DNR)-induced rats. Carvedilol was administered orally to the rats every day for 6 weeks at a cumulative dose of 9 mg/kg body weight DNR. DNR significantly induced cardiac damage and worsened cardiac function as well as increased cardiac mast cell density, elevating the myocardial protein and mRNA expression levels of tumor necrosis factor-α, vascular cell adhesion molecule-1, inter-cellular adhesion molecule-1, nuclear factor kappa-B, cyclooxygenase-2, monocyte chemotactic protein -1 and interleukin -6 compared to that in the control group. Cotreatment with carvedilol significantly attenuated the myocardial protein and mRNA expression levels of these inflammatory markers, decreased cardiac mast cell density, improved histological cardiac damage and cardiac functions. In conclusion, inflammation plays a significant role in DNR-induced cardiotoxicity, and carvedilol contributes to cardioprotection against inflammation-mediated cardiotoxicity in DNR-induced rats through its anti-inflammatory mechanism.